Most substance use disorders (SUD) treatment clinical trials are too short and small to reliably estimate the incidence of rare events like death. The aim of this study was to estimate the overall mortality rates among a SUD treatment-seeking population by pooling participants from multiple clinical trials conducted through the National Institute on Drug Abuse (NIDA)-sponsored National Drug Abuse Treatment Clinical Trials Network (CTN). Data were collected on 9,866 drug and/or alcohol users who sought treatment and participated in one of the CTN's 22 randomized clinical trials in national community treatment programs (CTPs) for SUD. Pooled analysis was performed to assess age- and gender-standardized mortality rates (SM rates), and mortality ratios (SM ratios) of CTN participants compared to the U.S. general population. Differences in mortality rates across different types of substance of abuse were also assessed.

The age- and gender-SM rate among CTN trials participants was 1403 (95% CI: 862-2074) per 100,000 person years (PY) compared to 542 (95% CI: 541-543) per 100,000 PY among the U.S. general population in 2005. By gender, age-adjusted SM ratio for female CTN trial participants was over five times (SM ratio=5.35, 95% CI: 3.31-8.19)), and for male CTN trial participants was over three times (SM ratio=3.39, 95% CI: 2.25-4.9) higher than their gender comparable peers in the U.S. general population. Consistent with the literature, overdose was the most frequently reported cause of death among CTN trial participants.

Conclusions: Age and gender-standardized mortality rates and ratios among NIDA CTN SUD treatment-seeking clinical trials participants are higher than the age and gender comparable U.S. general population. The overall mortality rates of CTN trials participants are similar to in-treatment mortality reported in large U.S. and non-U.S. cohorts of opioid users. Future analysis with additional CTN trial participants and risk times will improve the stability of estimates, especially within subgroups based on primary substance of abuse. These SUD mortality rates can be used to facilitate safety monitoring within SUD clinical trials by providing a potential reference in the future against which to assess rare death events in individual clinical trials. (Article (Peer-Reviewed), PDF, English, 2016)